The present invention relates to novel NMR principal detector elements that improve the resolution and line shape of NMR spectra obtained using toroid cavity detector NMR probes.
It is critical to improve the magnetic field homogeneity in toroid cavity detector NMR probes in order to make them widely accepted and used in the analytical and biochemistry communities. We have invented a passively shimmed principal detector element for toroid cavity probes for the purpose of improving the magnetic field homogeneity in the volume of space occupied by the sample.
The development of high-field Toroid Cavity Detectors (TCDs) for nuclear magnetic resonance (NMR) analyses of mass-limited biological samples is currently motivated by the promise of a substantial increase in sensitivity. However, the inhomogeneity of the external magnetic field (B0) over the sample volume in a TCD is a problem that results in reduced sensitivity. The purpose of the present invention is to improve B0 homogeneity in TCD NMR probes by introducing novel geometrical modifications to the principal detector element (central conductor).
The geometrical interface between two materials with dissimilar volume magnetic susceptibilities is known to cause magnetic field distortions in the NMR-active space. In TCDs the magnetic field distortion problem is due to the exterior and interior interfaces of the cylindrical cavity. The exterior air-copper interface at the top and bottom of the cavity causes distortions in the magnetic field that can be eliminated by elongating the cavity. The interior copper-sample interface at the top and bottom of the cavity also causes distortions in the magnetic field in the sample volume, but elongating the cavity cannot eliminate these distortions. We have invented passively shimmed principal detector elements that reduce magnetic field distortions caused by the interior interfaces at the top and bottom of the cavity. Passive shimming takes advantage of materials with different volume susceptibilities and geometrical forms to homogenize the magnetic field in a prescribed volume. The more commonly used approach to homogenize magnetic fields is the active shimming method. Active shimming requires energized magnet coils that generate correction fields. The magnet coils that are included in commercial NMR instruments were designed to homogenize the sample volume in commercial (Helmholtz-style) NMR probes, and are not capable of correcting magnetic field distortions caused by TCD probes. Magnet coils specifically designed for TCD probes are not available. Alternatively, a combination of different materials arranged in the cylindrical geometry of the TCD affords a passive approach to eliminating magnetic field distortions. A principal detector element of novel geometric designs contained within a TCD which eliminates distortions in the magnetic field in the sample volume is the subject of the present invention.
Three embodiments of a passively shimmed principal detector element in accordance with the present invention have been disclosed by the inventors and are as follows: (1) a cylindrical spool with surfaces that extend beyond the sample volume that is contained within a larger cylindrical cavity containing the sample, (2) susceptibility matching cylindrical plugs above and below the central conductor, and (3) a cylindrical central conductor with spheroid interfaces at both ends. These three devices use a combination of different materials and geometrical structures with cylindrical symmetry to improve the magnetic field homogeneity in TCD probes. We expect that a combination of active and passive shimming devices will be required to make the magnetic field homogeneity performance of TCD probes competitive with commercial NMR probes.
Nuclear magnetic resonance (NMR) analysis is a powerful method by which to determine chemical structures and to examine reaction dynamics in a diversity of chemical and biochemical systems. In particular, NMR analyses of chemical and biochemical systems using toroid cavity NMR detector probes afford the possibility of detecting very small sample quantities not normally analyzable with conventional NMR detector probes that are commercially available.
For example, U.S. Pat. No. 5,574,370, issued Nov. 12, 1996 to Woelk et al., discloses a toroid cavity detector (TCD) system for determining the spectral properties and spatial distance from a fixed axis for a sample using Nuclear Magnetic Resonance. The detection system consists of a toroid cavity with a central conductor oriented along the main axis of the toroidal cylinder and oriented parallel to a static uniform magnetic field, B0. A radio frequency (RF) signal is applied to the central conductor to produce a concentric magnetic field B1 perpendicular to the central axis of the toroid and whose field strength varies as the inverse of the radial position in the toroid. (The position of the center axis of the toroid cavity is the location of the zero position for the radial dimension and axis.) The toroid cavity detection system can be used to encapsulate a sample, or the detection system can be perforated to allow a sample to flow into the detection device or to place the samples in specified sample tubes. Flexible capillary tubing can also be wound about the central conductor and used to transfer and contain a sample or a series of samples. The central conductor can also be coated to determine the spectral property of the coating and the coating thickness. The sample is then subjected to the respective magnetic fields and the responses measured to determine the desired properties.
U.S. Pat. No. 6,046,592, issued Apr. 4, 2000 to Rathke et al., discloses a near-electrode imager for employing nuclear magnetic resonance imaging to provide in situ measurements of electrochemical properties of a sample as a function of distance from a working electrode, also know as the central conductor. The near-electrode imager uses the radio frequency field gradient within a cylindrical toroid cavity resonator to provide high-resolution nuclear magnetic resonance spectral information on electrolyte materials, electrode-electrolyte interphases, and electrode coating materials.
U.S. Pat. No. 6,191,583, issued Feb. 20, 2001 to Gerald II et al., discloses a toroid cavity detector that includes an outer cylindrical housing through which extends a wire along the central axis of the cylindrical housing from a closed bottom portion to the closed top end of the cylindrical housing. In order to analyze a sample placed in the housing, the housing is placed in an externally applied static main homogeneous magnetic field (B0). An RF current pulse is supplied through the wire such that an alternately energized and de-energized magnetic field (B1) is produced in the toroid cavity. The B1 field is oriented perpendicular to the B0 field. Following the RF current pulse, the response of the sample to the applied B0 field is detected and analyzed. In order to minimize the detrimental effect of probe ringing, the cylindrically shaped housing is elongated sufficiently in length so that the top and bottom portions are located in weaker, fringe areas of the static main magnetic B0 field. In addition, a material that tends to lessen the effect of probe ringing is positioned along the top and bottom ends of the toroid cavity. In another embodiment, a plug is positioned adjacent the inside of the top and bottom ends of the toroid cavity so that the sample contained in the toroid cavity is maintained in the strongest and most homogeneous region of the static magnetic B0 field.
U.S. Pat. No. 6,469,507, issued Oct. 22, 2002 to Gerald II et al., discloses imaging apparatus that is used in a toroid cavity detector for nuclear magnetic resonance (NMR) analysis to hold samples relative to a principal detector element which is a flat metal conductor, the plane of which is parallel to the longitudinal axis of the toroid cavity. A sample is held adjacent to or in contact with the principal detector element so that the sample can be subjected to NMR analysis when a static main homogeneous magnetic field (B0) produced by a NMR magnetic device is applied to the toroid cavity and an RF excitation signal pulse is supplied to the principal detector element so that an alternately energized and de-energized magnetic field (B1) is produced in the sample and throughout the toroid cavity. The sample may be components of a coin cell battery which are mounted within the toroid cavity relative to the principal detector element by a non-conductive coin cell battery imager or a press assembly so that the components are hermetically sealed together and so that a direct current potential can be applied to the components. Alternately, a sample is positioned within an O-ring maintained relative to the principal detector element by a pair of glass plates that are disposed on opposite sides of the principal detector element and are compressed towards each other so that NMR analysis can be used when light is transmitted through the sample or to analyze a sample separated from the principal detector element by semi-permeable membranes.
The subject matter of each of the aforementioned U.S. Pat. Nos. 5,574,370; 6,046,592; 6,191,583; and 6,469,507 is incorporated herein by reference.
A principal object of the present invention is to provide a novel principal NMR detector element that allows recording of undistorted NMR spectra using a toroid cavity NMR detector probe.
In brief, the novel principal NMR detector element of the present invention comprises the NMR-active inductance of a radio frequency (RF) resonance circuit. The RF resonance circuit includes a principal detector element, capacitor elements, and a cavity sample chamber. The principal detector element forms an inductor in the RF resonance circuit.
In one embodiment of the invention, the principal NMR detector element is comprised of two metallic hemispheres connected together by a metallic central rod to form the general shape of a dumbbell. Attaching each hemisphere to an opposed end of the rod and connecting this combination to an RF circuit allows the combination to function as the inductor of the NMR RF circuit.
More specifically, a cylindrical tube is fitted and extended over both hemispheres to form a gas-tight volume (the sample volume) bounded by the flat bottoms of the hemispheres and the outer surface of the rod. The sample fully or partially fills the sample volume. The geometry and material of the hemispheres are chosen and designed according to the arrangement of the fluid or fluids disposed within the sample volume so that a uniform static magnetic field fills the sample volume when the fluid(s) are surrounding the principal detector element.